The Hedgehog (Hh) signaling pathway normally functions during embryogenesis to direct cellular differentiation and proliferation and in adult tissue homeostasis, and tissue repair in the presence of chronic inflammation. Mutations in Hh and its downstream signaling components are associated with a number of diseases. For example, aberrant activation of the Hh pathway is involved in certain cancers, including basal cell carcinoma (BCC) and medulloblastoma. Recent results show that inhibitors of Hh signaling induced the regression of medulloblastoma allografts and arrested proliferation of basal cells within BCC-like lesions and led to regression of the lesions.
An important component in the Hh signaling pathway is the seven-pass transmembrane protein Smoothened (Smo). Smo is a downstream activator in the Hh pathway and may be upregulated in certain cancers such as BCC. As such, compounds capable of inhibiting Smo may be useful in treating disorders in which Hh and/or Smo signaling is upregulated. Moreover, Smo inhibitors may also be useful for studying Hh regulated biology.